Abstract

Background

Genes in a functional pathway can have complex interactions. A gene might activate
or suppress another gene, so it is of interest to test joint associations of gene
pairs. To simultaneously detect the joint association between disease and two genes
(or two chromosomal regions), we propose a new test with the use of genomic similarities.
Our test is designed to detect epistasis in the absence of main effects, main effects
in the absence of epistasis, or the presence of both main effects and epistasis.

Results

The simulation results show that our similarity test with the matching measure is
more powerful than the Pearson's χ2 test when the disease mutants were introduced at common haplotypes, but is less powerful
when the disease mutants were introduced at rare haplotypes. Our similarity tests
with the counting measures are more sensitive to marker informativity and linkage
disequilibrium patterns, and thus are often inferior to the similarity test with the
matching measure and the Pearson's χ2 test.

Conclusions

In detecting joint associations between disease and gene pairs, our similarity test
is a complementary method to the Pearson's χ2 test.